A Novel Monoclonal Antibody Targeting a Large Surface of the Receptor Binding Motif Shows Pan-neutralizing SARS-CoV-2 Activity Including BQ.1.1 Variant

de Campos-Mata, L.; Trinite, B.; Modrego, A.; Tejedor Vaquero, S.; Pradenas, E.; Rodrigo Melero, N.; Carlero, D.; Marfil, S.; Pons-Grifols, A.; Bueno-Carrasco, M. T.; Santiago, C.; Tarres-Freixas, F.; Urrea, V.; Izquierdo, N.; Riveira-Munoz, E.; Ballana, E.; Perez, M.; Vergara-Alert, J.; Segales, J.; Carolis, C.; Arranz, R.; Blanco, J.; Magri, G.

doi:10.1101/2023.01.20.524748

Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.01.20.524748

A Novel Monoclonal Antibody Targeting a Large Surface of the Receptor Binding Motif Shows Pan-neutralizing SARS-CoV-2 Activity Including BQ.1.1 Variant

View original source ↗Export metadata ↓

Abstract

In the present study we report the functional and structural characterization of 17T2, a new highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody (mAb) isolated from a convalescent COVID-19 individual infected during the first wave of the COVID-19 pandemic. 17T2 is a class 1 VH1-58/{kappa}3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA memory B cell and developed as a human recombinant IgG1. Functional characterization revealed that 17T2 mAb has a high and exceptionally broad neutralizing activity against all SARS-CoV-2 spike variants tested, including BQ.1.1. Moreover, 17T2 mAb has in vivo prophylactic activity against Omicron BA.1.1 infection in K18-hACE2 transgenic mice. 3D reconstruction from cryogenic-electron microscopy (cryo-EM) showed that 17T2 binds the Omicron BA.1 spike protein with the RBD domains in "up" position and recognizes an epitope overlapping with the receptor binding motif, as it is the case for other structurally similar neutralizing mAbs, including S2E12. Yet, unlike S2E12, 17T2 retained its high neutralizing activity against all Omicron sublineages tested, probably due to a larger contact area with the RBD, which could confer a higher resilience to spike mutations. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 mAb as a potential candidate for future therapeutic and prophylactic interventions.

Explore related subjects

immunology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

de Campos-Mata, L., Trinite, B., Modrego, A., Tejedor Vaquero, S., Pradenas, E., Rodrigo Melero, N., Carlero, D., Marfil, S., Pons-Grifols, A., Bueno-Carrasco, M. T., Santiago, C., Tarres-Freixas, F., Urrea, V., Izquierdo, N., Riveira-Munoz, E., Ballana, E., Perez, M., Vergara-Alert, J., Segales, J., Carolis, C., Arranz, R., Blanco, J., Magri, G.. 2023-01-23. A Novel Monoclonal Antibody Targeting a Large Surface of the Receptor Binding Motif Shows Pan-neutralizing SARS-CoV-2 Activity Including BQ.1.1 Variant. https://doi.org/10.1101/2023.01.20.524748

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Proliferation and mutation as humoral immune response

The affinity maturation process, through which antibodies acquire relatively high affinity for an invading pathogen, involves complex mechanisms whose relative importance is not yet fully understood. This study proposes an analytical model of this process, to investigate the main factors governing proliferation and mutation and assess their respective roles. The model suggests that the immune system should not be expected to follow a single, rigid evolutionary pattern, as a wide range of proliferation and mutation strategies can yield nearly optimal outcomes. Keywords: Antibody, antigen, affinity, B-cell, mutation, proliferation

immunology↗

bioRxiv2026

Proteome-wide discovery of novel diagnostic antigens for coccidioidomycosis

Coccidioidomycosis, commonly called Valley Fever (VF), caused by Coccidioides spp., is an understudied fungal disease that accounts for a substantial fraction of pneumonias in endemic areas. Diagnosis remains challenging because the mainstay of diagnosis is serology, and current assays have modest sensitivity in early infection. Discovery of new antigens could improve serologic detection early in disease. Here, we use PepSeq, a DNA-programmable serology platform, to represent the complete proteome of Coccidioides within a library of 244,000 DNA-barcoded peptides. By profiling antibody reactivity at the protein and epitope levels in VF patients, naturally infected pigtail macaques, and healthy controls, we identify numerous previously-unrecognized antigens and epitopes, including some shared between humans and macaque responses. When translated into a pooled peptide ELISA, we show that a subset of identified antigens can discriminate VF cases from controls in an independent cohort with high accuracy (AUC = 0.91). These findings establish high-dimensional peptide serology as a scalable approach for fungal antigen discovery and identify new targets for improved VF diagnosis.

immunology↗

bioRxiv2026

Establishing an ex vivo platform for molecular profiling of skin structural cells using frozen human skin biopsies

Skin structural cells, including keratinocytes, melanocytes, endothelial cells, and fibroblasts, play critical roles in the development of chronic inflammatory skin disease. Inflammatory stimuli induce transcriptional reprogramming and epigenetic changes in skin structural cells, which contribute to disease pathogenesis. Although two-dimensional (2D) and three-dimensional (3D) skin culture models have been widely used to investigate inflammatory responses in skin structural cells, ex vivo systems that maintain skin structure and cellular composition remain limited. To address this gap, we explored using frozen skin biopsies as an experimental platform to study the responses of skin structural cells to inflammatory stimuli. Using a simple air-liquid interface culture method on permeable Transwell inserts, we showed that viable skin structural cells that retain cell-type-specific transcriptional profiles can be recovered from frozen skin biopsies after prolonged in vitro culture. Stimulation with IFN-{gamma} induced robust transcriptional and chromatin accessibility changes that were largely resolved after stimulus removal, with transcriptional responses to secondary stimulation comparable to the primary stimulation. Treatment of cultured skin biopsies with histone-modifying enzyme inhibitors effectively altered global histone modification levels, but did not substantially affect the transcriptional resolution of IFN-{gamma}-induced responses. Collectively, these findings establish cryopreserved human skin biopsies as a scalable ex vivo platform that enables mechanistic studies of inflammatory responses of multiple populations of skin structural cells.

immunology↗